Clinical relevance of monitoring serum adalimumab levels in axial spondyloarthritis.


Por: Senabre Gallego JM, Rosas J, Marco-Mingot M, García-Gómez JA, Santos-Soler G, Salas-Heredia E, Pons-Bas A, Barber-Vallés X, Bernal-Vidal JA, Cano-Pérez C, García-Carrasco M, Flores-Pardo E and AIRE-MB Group

Publicada: 1 may 2019 Ahead of Print: 21 mar 2019
Resumen:
Our aim was to assess the relationship between serum adalimumab levels, anti-drug antibodies (ADA) and disease activity in patients with axial spondylarthritis (SpA). We have carried out a single-centre cross-sectional study. adalimumab and ADA levels were analysed with ELISA and correlated with SpA activity using BASDAI and ASDAS scores. Adalimumab cut-off value was calculated to discriminate inactive disease/low disease activity (BASDAI < 4; ASDAS < 2.1) from moderate/high disease activity (BASDAI = 4; ASDAS = 2.1), using a receiver operating characteristic (ROC) curve. Up to January 2016, 51 consecutive patients were included. The median (range) age was 46.6 (18-68) and 47.1% were women. ADA prevalence was 27.5%, with none detected in the 21.6% receiving concomitant disease-modifying antirheumatic drugs (DMARDs) (p = 0.021). Adalimumab level was normal (> 3 mg/l) in 36 patients (70.6%), all without ADA. Fifteen patients (29.4%) had subtherapeutic adalimumab levels (< 3 mg/l), with ADA in 14 (93%). Median adalimumab (mg/l) was significantly higher in patients with inactive disease/low disease activity: BASDAI < 4 vs = 4: 9.5 vs 2.6 (p < 0.01); ASDAS-CRP < 2.1 vs = 2.1: 9.3 vs 0.3 (p < 0.001); ASDAS-ESR < 2.1 vs = 2.1: 9.9 vs 3.0 (p < 0.001), and this finding was consistent with the result of the multivariate model. Patients with inactive disease/low disease activity presented significantly lower ADA levels. The adalimumab level cut-offs and area under the curve (AUC) obtained in the ROC curves were: ASDAS-CRP (< 2.1) 4.6 mg/l (AUC 81.2%; 95% CI 67.5-94.9; p < 0.001); ASDAS-ESR (< 2.1) 7.7 mg/l (AUC 82.4%; 95% CI 69.3-95.5; p < 0.001); BASDAI (< 4) 6.4 mg/l (AUC 73.5%; 95% CI 58.6-88.3; p < 0.01). In conclusion, presence of ADA in axial SpA patients treated with adalimumab was associated with lower serum drug levels. ADA levels were lower and adalimumab levels were higher in patients with inactive disease/low disease activity based on BASDAI and ASDAS indices. Concomitant treatment with MTX reduces de likelihood of finding ADA. Serum adalimumab levels above 4.6 mg/l are recommended to avoid compromising efficacy.

Filiaciones:
Senabre Gallego JM:
 Sección de Reumatología, Hospital Marina Baixa, Av. Alcalde En Jaume Botella Mayor 7, 03570, Villajoyosa, Alicante, Spain.

Rosas J:
 Sección de Reumatología, Hospital Marina Baixa, Av. Alcalde En Jaume Botella Mayor 7, 03570, Villajoyosa, Alicante, Spain

Marco-Mingot M:
 Laboratory Department, Hospital Marina Baixa, Villajoyosa, Alicante, Spain

García-Gómez JA:
 Infectious Disease Department, Hospital General Universitario de Elche, Elche, Alicante, Spain

Santos-Soler G:
 Sección de Reumatología, Hospital Marina Baixa, Av. Alcalde En Jaume Botella Mayor 7, 03570, Villajoyosa, Alicante, Spain

Salas-Heredia E:
 Sección de Reumatología, Hospital Marina Baixa, Av. Alcalde En Jaume Botella Mayor 7, 03570, Villajoyosa, Alicante, Spain

Pons-Bas A:
 Sección de Reumatología, Hospital Marina Baixa, Av. Alcalde En Jaume Botella Mayor 7, 03570, Villajoyosa, Alicante, Spain

Barber-Vallés X:
 Center of Operations Research, Universitas Miguel Hernández, Elche, Alicante, Spain

:
 Sección de Reumatología, Hospital Marina Baixa, Av. Alcalde En Jaume Botella Mayor 7, 03570, Villajoyosa, Alicante, Spain

Cano-Pérez C:
 Sección de Reumatología, Hospital Marina Baixa, Av. Alcalde En Jaume Botella Mayor 7, 03570, Villajoyosa, Alicante, Spain

García-Carrasco M:
 Systemic Autoimmune Disease Research Unit, HGR-36-CIBIOR IMSS, Puebla, Mexico

 Department of Rheumatology and Immunology, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico

:
 Clinical Medicine Department, Universitas Miguel Hernández, Elche, Alicante, Spain
ISSN: 01728172





RHEUMATOLOGY INTERNATIONAL
Editorial
SPRINGER HEIDELBERG, TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY, Alemania
Tipo de documento: Article
Volumen: 39 Número: 5
Páginas: 841-849
WOS Id: 000466048800009
ID de PubMed: 30899987

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